madman
Super Moderator
ABSTRACT
Cardiovascular disease (CVD) is the leading cause of death in women aged 65 years and older. Sex hormones have been implicated as having a critical role in the evolution of CVD, with the focus mainly on estrogens in women. Available data also indicate that low testosterone blood levels may be detrimental to cardiovascular function in women. At blood concentrations considered normal for premenopausal women, testosterone has favorable effects on blood vessel function (relaxation and contraction), much of which is determined by the endothelial cells that line the inside of blood vessels. Testosterone enhances endothelium-dependent and independent brachial artery vasodilation and has an acute systolic blood pressure-lowering effect in postmenopausal women. Advantageous effects of testosterone in animal models have been seen for myocardial function and cardiac electrical signaling. Human data are mainly limited to observational and mechanistic studies, which mostly demonstrate beneficial effects of testosterone on cardiovascular health. Few studies of testosterone use in women, with cardiovascular endpoints as primary outcomes, have been published.
Data from clinical trials
Few clinical trials have examined the effects of testosterone on CVD risk markers or cardiovascular events as primary outcomes. Most of the available data come from randomized controlled trials (RCTs) of testosterone for the treatment of hypoactive sexual desire dysfunction, or other conditions. Our systematic review and meta-analysis of published clinical trials with treatment of testosterone and comparator for a duration of at least 3months revealed that oral testosterone therapy lowers total cholesterol, HDL-cholesterol and triglycerides, whereas non-oral testosterone therapy has no effect on lipid and lipoproteins [67]. Meta-analysis showed no influence of transdermal testosterone therapy on blood pressure, glucose, insulin or C-reactive protein [67]. Analysis of data from seven published RCTs of the transdermal testosterone patch [68–74], and two unpublished testosterone patch RCTs, showed no increase in myocardial infarction, stroke or venous thromboembolic events with testosterone compared with placebo [67]. In a 6-month pilot double-blind RCT of women, mean age 69years, with heart failure with reduced ejection fraction, testosterone therapy improved VO2max, performance on the 6-min walk test and insulin sensitivity [75]. No studies in women with HFpEF have been reported. However, we are presently recruiting women with asymptomatic HFpEF to determine the effects of testosterone versus placebo on VO2max and myocardial structure and function. In doses that approximate physiological concentrations for premenopausal women, testosterone has not been associated with serious adverse events [67].
Conclusions
The world has an aging population, with an over-representation of older women. CVD is not only a cause of personal disability but incurs enormous health-care costs. Understanding the factors that keep women healthy as they age is vital, considering the average life expectancy of a girl born in 2030 is likely to be greater than 90 years [76]. Sex hormones influence cardiovascular health, but compared with estrogens, testosterone has been overlooked as a hormone with favorable cardiovascular effects in women. The restoration of testosterone concentrations in older women to levels seen in younger women provokes thought as to why this occurs [3,11,13,14]. While available data from observational and mechanistic studies suggest this physiological change may afford cardiovascular protection, RCTs examining the cardiovascular effects of testosterone in women are scant. The findings from this review indicates that robust RCTs to determine the effects of testosterone in women with heart failure, both heart failure with reduced ejection fraction and HFpEF, and at increased atherogenic CVD risk are warranted.
Cardiovascular disease (CVD) is the leading cause of death in women aged 65 years and older. Sex hormones have been implicated as having a critical role in the evolution of CVD, with the focus mainly on estrogens in women. Available data also indicate that low testosterone blood levels may be detrimental to cardiovascular function in women. At blood concentrations considered normal for premenopausal women, testosterone has favorable effects on blood vessel function (relaxation and contraction), much of which is determined by the endothelial cells that line the inside of blood vessels. Testosterone enhances endothelium-dependent and independent brachial artery vasodilation and has an acute systolic blood pressure-lowering effect in postmenopausal women. Advantageous effects of testosterone in animal models have been seen for myocardial function and cardiac electrical signaling. Human data are mainly limited to observational and mechanistic studies, which mostly demonstrate beneficial effects of testosterone on cardiovascular health. Few studies of testosterone use in women, with cardiovascular endpoints as primary outcomes, have been published.
Data from clinical trials
Few clinical trials have examined the effects of testosterone on CVD risk markers or cardiovascular events as primary outcomes. Most of the available data come from randomized controlled trials (RCTs) of testosterone for the treatment of hypoactive sexual desire dysfunction, or other conditions. Our systematic review and meta-analysis of published clinical trials with treatment of testosterone and comparator for a duration of at least 3months revealed that oral testosterone therapy lowers total cholesterol, HDL-cholesterol and triglycerides, whereas non-oral testosterone therapy has no effect on lipid and lipoproteins [67]. Meta-analysis showed no influence of transdermal testosterone therapy on blood pressure, glucose, insulin or C-reactive protein [67]. Analysis of data from seven published RCTs of the transdermal testosterone patch [68–74], and two unpublished testosterone patch RCTs, showed no increase in myocardial infarction, stroke or venous thromboembolic events with testosterone compared with placebo [67]. In a 6-month pilot double-blind RCT of women, mean age 69years, with heart failure with reduced ejection fraction, testosterone therapy improved VO2max, performance on the 6-min walk test and insulin sensitivity [75]. No studies in women with HFpEF have been reported. However, we are presently recruiting women with asymptomatic HFpEF to determine the effects of testosterone versus placebo on VO2max and myocardial structure and function. In doses that approximate physiological concentrations for premenopausal women, testosterone has not been associated with serious adverse events [67].
Conclusions
The world has an aging population, with an over-representation of older women. CVD is not only a cause of personal disability but incurs enormous health-care costs. Understanding the factors that keep women healthy as they age is vital, considering the average life expectancy of a girl born in 2030 is likely to be greater than 90 years [76]. Sex hormones influence cardiovascular health, but compared with estrogens, testosterone has been overlooked as a hormone with favorable cardiovascular effects in women. The restoration of testosterone concentrations in older women to levels seen in younger women provokes thought as to why this occurs [3,11,13,14]. While available data from observational and mechanistic studies suggest this physiological change may afford cardiovascular protection, RCTs examining the cardiovascular effects of testosterone in women are scant. The findings from this review indicates that robust RCTs to determine the effects of testosterone in women with heart failure, both heart failure with reduced ejection fraction and HFpEF, and at increased atherogenic CVD risk are warranted.
